Acclimatization: prolonged exposure to altitude

When people are exposed to altitude over days, weeks, and months, their bodies gradually adjust to the lower oxygen partial pressure in the air. But, however well they acclimatize to the conditions at high altitude, they never fully compensate for the hypoxia. Even endurance-trained athletes who live at altitude for years never attain the level of performance or the VO2max values that they might achieve at sea level. In this regard, acclimatization to altitude is similar to heat acclimation. Heat acclimation improves performance and attenuates physiological strain during exercise in the heat compared to that experienced during the first few days; however, performance is still poorer than in cooler environments.

The following sections cover some of the physiologica adaptations that occur with prolonged altitude exposure. These include changes at the pulmonary, cardiovascular, and muscle tissue(cellular) level. In general, these adaptations take longer to fully develop(several weeks to several months) than those associated with heat acclimation(typically one to two weeks). Generally, about three weeks are needed for full acclimatization to even moderate altitude. For each additional 600m(1,970ft) altitude increase, another week is needed an average. All of these beneficial effects are lost within a month of return to sea level.

Pulmonary adaptations

One of most important adaptations to altitude is an increase in pulmonary ventilation, both at rest and during exercise. Within three or four days at 4,000m(13,123ft), the increased resting ventilation rate levels off at a value about 40% higher than at sea level. Submaximal exercise ventilatory rate also plateaus at about 50% higher but over a longer time frame. Increases in ventilation during exercise remain elevated at altitude and are more pronounced at higher exercise intensities.

Blood adaptations

During the first two weeks at altitude, the number of circulating erythrocytes increase. The lack of oxygen at altitude stimulates the renal release of EPO. Within the first 3h after the athlete arrives at a high elevation, the blood’s EPOconcentration increases; it then continues to increase for two to three days. Although blood EPO concentrations return to baseline levels about a month, the polycythemia(increased red blood cells) may be evident for three months or more. After a person lives at 4,000m(13,123ft) for about six months, his or her total blood volume(composed mainly of the red cell volume and the plasma volume) increases by about 10% not only as a result of the altitude – induced stimulation of eryhtrocite production but also because of plasma volume expansion.

The percentage of total blood volume composed of erythrocytes is reffered to as the hematocrit. Residents in the central Andes of Peru(4,540m, or 14,895ft) have an average hematocrit of sea-level residents, which is only 45% to 48%. However, during six weeks of exposure to the Peruvian altitude, sea-level residents have shown remarkable increases in their hematocrit levels, up to an average of 59%.

As the volume of erythrocytes increases, so does the blood’s hemoglobin content. As noted in the figure below, blood hemoglobin concentration needs to increase proportionately with increases in the elevation at which people reside. The data presented are for men. For women, however, the limited available data show a similar trend but with a lower concentration than for men at a given altitude. These adaptations improve the oxygen-carrying capacity of a fixed volume of blood.

The reduction in plasma volume during acute altitude exposure reduces total blood volume, thus reducing submaximal and maximal cardiac output. But with acclimatization, as plasma volume increases over several weeks at altitude as red blood cells continue to increase, maximal cardiac output increases. However, it does not return to sea-level values. Thus, overall oxygen delivery capacity is increased with acclimatization but not to the extent needed to achieve sea-level VO₂max values.

There is some debate about whether acclimatization alters oxygen transport in the blood by changing the shape and position of the oxyhemoglobin dissociation curve(picture below). The concentration of 2,3-diphosphoglycerate(2,3-DPG) increases in red blood cells, which shifts the curve to the right. This would favor unloading of oxygen at the tissues(because more oxygen would be unloading from hemoglobin at any given low arteral PO₂), but this effect opposes the loading benefit of the respiratory alkalosis, a leftward shift. The net effect of both mechanisms is variable.

Muscle adaptations

Although few attempts have been made to study muscle changes that occur during exposure to altitude, sufficient muscle biopsy data exist to indicate that muscles undergo significant structural and metabolic changes during ascent to altitude. Table below summarizes some of the muscle adaptations that occurred over a four-to-six-week period of chronic hypoxia during expeditions to Mount Everest and Mount McKinley. Muscle fiber cross-sectional area decreased, thus decreasing total muscle area. Capillary density in the muscles increased, which allowed more blood and oxygen to be delivered to the muscle fibers. Muscles’ inability to meet exercise demands at high altitude might be related to a decrease in their mass and their ability to generate ATP.

Approximate changes in muscle structure and metabolic potential during four to six weeks of chronic hypoxia
Muscle characteristic	Direction of change	% change
Muscle area	decreased	12
Type II(slow-twitch) fibers	decreased	20-25
Type I(fast-twitch) fibers	decreased	20
Capillary density(capillaries per mm2)	increased	15
Succinate dehydrogenase	decreased	25
Citrate synthase	decreased	20
Phosphorylase	decreased	30
Phosphofructokinase	decreased	50

The cause of the decreased muscle cross-sectional area within the first days and weeks at altitude is not fully understood. Prolonged exposure to high altitude frequently causes a loss of appetite and a noticeable weight loss. During a 1992 expedition to climb Mount McKinley, six men experienced an average weight loss of 6kg, or 13lb(D. L. Costill et al., unpublished data). Although part of this loss represents a general decrease in body weight and extracellular water, all of the men experienced a noticeable decrease in muscle mass. It seems logical to assume that much of this decrease in muscle mass is associated with loss of appetite and a wasting of muscle protein. Perhaps future studies on nutrition and body composition in mountain climbers will provide a more thorough explanation of the incapacitating influences of high altitude on muscle structure and function.

Several weeks at altitudes above 2,500m(8,202ft) reduce the metabolic potential of muscle, although this may not occur at lower elevations. Also presented in the table above, are data from experiments performed on Mount McKinley and Mount Everest showing that mitochondrial function and glycolytic enzyme activities of the leg muscles(vastus lateralis and gastrocnemius) are significantly reduced after four weeks at altitude. This suggests that, in addition to receiving less oxygen, muscles lose some of their capacity to perform oxidative phosphorylation and generate ATP. Unfortunately, no muscle biopsy data have been obtained from long-term residents at high altitudes to determine whether those individuals experience any muscular adaptations as a consequence of lifelong residence at these elevations.